Class Of Transcription Factors Research Articles

A SlMYB75-centred transcriptional cascade regulates trichome formation and sesquiterpene accumulation in tomato.

Tomato trichomes act as a mechanical and chemical barrier against pests. An R2R3 MYB transcription factor gene, SlMYB75, is highly expressed in type II, V, and VI trichomes. SlMYB75 protein is located in the nucleus and possesses transcriptional activation activity. Down-regulation of SlMYB75 increased the formation of type II, V, and VI trichomes, accumulation of δ-elemene, β-caryophyllene, and α-humulene in glandular trichomes, and tolerance to spider mites in tomato. In contrast, overexpression of SlMYB75 inhibited trichome formation and sesquiterpene accumulation, and increased plant sensitivity to spider mites. RNA-Seq analyses of the SlMYB75 RNAi line indicated massive perturbation of the transcriptome, with a significant impact on several classes of transcription factors. Expression of the MYB genes SlMYB52 and SlTHM1 was strongly reduced in the RNAi line and increased in the SlMYB75-overexpressing line. SlMYB75 protein interacted with SlMYB52 and SlTHM1 and activated their expression. SlMYB75 directly targeted the promoter of the cyclin gene SlCycB2, increasing its activity. The auxin response factor SlARF4 directly targeted the promoter of SlMYB75 and inhibited its expression. SlMYB75 also bound to the promoters of the terpene synthase genes SlTPS12, SlTPS31, and SlTPS35, inhibiting their transcription. Our findings indicate that SlMYB75 perturbation affects several transcriptional circuits, resulting in altered trichome density and metabolic content.

Molecular mechanisms of fat deposition: IL-6 is a hub gene in fat lipolysis, comparing thin-tailed with fat-tailed sheep breeds.

Tail fat content affects meat quality and varies significantly among different breeds of sheep. Ghezel (fat-tailed) and Zel (thin-tailed) are two important Iranian local sheep breeds with different patterns of fat storage. The current study presents the transcriptome characterization of tail fat using RNA sequencing in order to get a better comprehension of the molecular mechanism of lipid storage in the two mentioned sheep breeds. Seven (Zel 4 and Ghezel 3) 7-month-old male lambs were used for this experiment. The results of sequencing were analyzed with bioinformatics methods, including differentially expressed genes (DEGs) identification, functional enrichment analysis, structural classification of proteins, protein–protein interaction (PPI) and network and module analyses. Some of the DEGs, such as LIPG, SAA1, SOCS3, HIF-1 , and especially IL-6, had a close association with lipid metabolism. Furthermore, functional enrichment analysis revealed pathways associated with fat deposition, including “fatty acid metabolism”, “fatty acid biosynthesis” and “HIF-1 signaling pathway”. The structural classification of proteins showed that major down-regulated DEGs in the Zel (thin-tailed) breed were classified under transporter class and that most of them belonged to the solute carrier transporter (SLC) families. In addition, DEGs under the transcription factor class with an important role in lipolysis were up-regulated in the Zel (thin-tailed) breed. Also, network analysis revealed that IL-6 and JUNB were hub genes for up-regulated PPI networks, and HMGCS1, VPS35 and VPS26A were hub genes for down-regulated PPI networks. Among the up-regulated DEGs, the IL-6 gene seems to play an important role in lipolysis of tail fat in thin-tailed sheep breeds via various pathways such as tumor necrosis factor (TNF) signaling and mitogen-activated protein kinase (MAPK) signaling pathways. Due to the probable role of the IL-6 gene in fat lipolysis and also due to the strong interaction of IL-6 with the other up-regulated DEGs, it seems that IL-6 accelerates the degradation of lipids in tail fat cells.

Genome-wide identification and expression analysis of the MADS-box transcription factor family in Camellia sinensis.

The MADS-box genes are an important class of transcription factors and play critical roles in flower development. However, the functions of these genes in the economically important drinking plant, Camellia sinensis, are still not reported. Here, an evolutionary analysis of tea MADS-box genes was performed at whole genome level. A total of 83 MADS-box genes were identified in tea, and their gene structures and expression patterns were further analyzed. The tea MADS-box genes were classified into Mα (26), Mβ (12), Mγ (9), MIKC* (7), and MIKCC (29) clade according to their phylogenetic relationship with Arabidopsis thaliana. Several cis-elements were identified in the promoter regions of the CsMADS genes that are important in regulating growth, development, light responses, and the response to several stresses. Most CsMADS genes display clear different expression patterns in different organs and different species of tea plant. The expression of CsMADS genes can be regulated by abiotic stresses and phytohormone treatment. Our results lay the foundation for future research on the function of CsMADS genes and beneficial for improving tea agricultural traits in the future.

Mutational processes in cancer preferentially affect binding of particular transcription factors

Protein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial progress in dissecting the patterns of mutations, i.e., the "mutational signatures", generated by different mutational processes. By combining these two layers of information we can investigate whether certain mutational processes tend to preferentially affect binding of particular classes of TFs. Such preferential alterations of binding might predispose to particular oncogenic pathways. We developed and implemented a method, termed "Signature-QBiC", that integrates protein binding microarray data with the signatures of mutational processes, with the aim of predicting which TFs’ binding profiles are preferentially perturbed by particular mutational processes. We used Signature-QBiC to predict the effects of 47 signatures of mutational processes on 582 human TFs. Pathway analysis showed that binding of TFs involved in NOTCH1 signaling is strongly affected by the signatures of several mutational processes, including exposure to ultraviolet radiation. Additionally, toll-like-receptor signaling pathways are also vulnerable to disruption by this exposure. This study provides a novel overview of the effects of mutational processes on TF binding and the potential of these processes to activate oncogenic pathways through mutating TF binding sites.

The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress.

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

Identification and characterization of MADS box gene family in pigeonpea for their role during floral transition.

The online version contains supplementary material available at 10.1007/s13205-020-02605-7.

Nuclear Factor-Y (NF-Y), the Key Player in Plant Growth and Development: Prediction and Characterization of Vanilla planifolia

Background: V. planifolia is of tremendous commercial importance as a source of an important flavor, vanilla, which is the backbone of the culinary and perfumery industry. Hence, efforts to ease cultivation and promote growth in this plant are the need of the hour. Nuclear factor-Y (NF-Y) gene family, a class of vital transcription factors, plays a pivotal role in a large number of developmental processes. Objectives: The present study aims to identify and characterize NF-Y gene family in Vanilla planifolia which would bring insights to their role as key factors promoting growth and development in this orchid. Methods: Physico-chemical characterization, protein structure prediction and interaction, the establishment of evolutionary relationship and expression profiling were attempted using various in silico tools. Results: Twenty five putative NF-Y members were identified in Vanilla planifolia, which were further classified into three sub-classes, NF-YA (13), NF-YB (7) and NF-YC (5), on the basis of specific domains and conserved regions. Prediction of three-dimensional structure was done on the basis of structural similarity with NF-Y structure templates. Evolutionary analysis of the NF-Ys of Arabidopsis thaliana and Oryza sativa classified these into three major clusters, which indicated the similarity of functions. Variable expression of VpNF-Y genes confirmed their role in diverse functions. VpNF-YA genes generally showed higher expression in vegetative tissues, while a few VpNF-YBs showed seed-specific expression. Protein-protein interaction indicated complex formation for optimum function. Conclusions: This work paves way for further functional characterization of NF-Y genes in Vanilla planfolia.

A novel transcription factor negatively regulates antioxidant response, cell wall integrity and virulence in the fungal insect pathogen, Beauveria bassiana.

Genomic data have identified a class of fungal specific transcription factors (FsTFs) that are thought to regulate unique aspects of fungal gene expression, although the functions of many of these proteins remain unknown. Here, a novel FsTF (BbStf1), which features a leucine zipper dimerization domain and a fungal transcription factor regulatory middle homology region, was characterized in Beauveria bassiana, a filamentous insect fungal pathogen. Transcriptional activation and nuclear localization were experimentally confirmed for BbStf1. Disruption of Bbstf1 resulted in increased tolerance to oxidative stress and cell wall perturbation, accompanied by increased peroxidase (POD) and superoxide dismutase (SOD) activities and ratio of reduced/oxidized glutathione (GSH/GSSG), and by thickened cell wall and altered composition. Gene expression profile analysis revealed that transcription patterns of antioxidant enzyme and cell wall integrity-involved genes were altered in the ∆Bbstf1, including some BbStf1-targeted genes clarified with evidence. The ∆Bbstf1 strain displayed greater virulence to Galleria mellonella in the bioassays through both topical infection and intrahaemocoel injection due to more rapid proliferation in the haemocoel as compared to the wild-type strain. Altogether, BbStf1 acts as a negative regulator of antioxidant response, cell wall integrity and virulence in B. bassiana.

Remodeling the chromatin landscape in T lymphocytes by a division of labor among transcription factors

An extraordinary degree of condensation is required to fit the eukaryotic genome inside the nucleus. This compaction is attained by first coiling the DNA around structures called nucleosomes. Mammalian genomes are further folded into sophisticated three-dimensional (3D) configurations, enabling the genetic code to dictate a diverse range of cell fates. Recent advances in molecular and computational technologies have enabled the query of higher-order chromatin architecture at an unprecedented resolution and scale. In T lymphocytes, similar to other developmental programs, the hierarchical genome organization is shaped by a highly coordinated division of labor among different classes of sequence-specific transcription factors. In this review, we will summarize the general principles of 1D and 3D genome organization, introduce the common experimental and computational techniques to measure the multilayer chromatin organization, and discuss the pervasive role of transcription factors on chromatin organization in T lymphocytes.

Overexpression of a Pak Choi Gene, BcAS2, Causes Leaf Curvature in Arabidopsis thaliana.

The LBD (Lateral Organ Boundaries Domain) family are a new group of plant-specific genes, which encode a class of transcription factors containing conserved Lateral Organization Boundary (LOB) domains, and play an important role in regulating the adaxial–abaxial polarity of plant leaves. In Arabidopsis thaliana, ASYMMETRIC LEAVES 2 (AS2) has a typical LOB domain and is involved in determining the adaxial cell fate. In this study, we isolated the BcAS2 gene from the pak choi cultivar “NHCC001”, and analyzed its expression pattern. The results showed that the BcAS2 encoded a protein made up of 202 amino acid residues which were located in the nucleus and cytomembrane. The Yeast two-hybrid system (Y2H) assay indicated that BcAS2 interacts with BcAS1-1 and BcAS1-2 (the homologous genes of AS1 gene in pak choi). In the transgenic Arabidopsis thaliana that overexpressed BcAS2 gene, it presented an abnormal phenotype with a curly shape. Taken together, our findings not only validate the function of BcAS2 in leaf development in Arabidopsis thaliana, but also contribute in unravelling the molecular regulatory mechanism of BcAS2, which fulfills a special role by forming complexes with BcAS1-1/2 in the establishment of the adaxial–abaxial polarity of the lateral organs in pak choi.

CTCF As an Example of DNA-Binding Transcription Factors Containing Clusters of C2H2-Type Zinc Fingers.

In mammals, most of the boundaries of topologically associating domains and all well-studied insulators are rich in binding sites for the CTCF protein. According to existing experimental data, CTCF is a key factor in the organization of the architecture of mammalian chromosomes. A characteristic feature of the CTCF is that the central part of the protein contains a cluster consisting of eleven domains of C2H2-type zinc fingers, five of which specifically bind to a long DNA sequence conserved in most animals. The class of transcription factors that carry a cluster of C2H2-type zinc fingers consisting of five or more domains (C2H2 proteins) is widely represented in all groups of animals. The functions of most C2H2 proteins still remain unknown. This review presents data on the structure and possible functions of these proteins, using the example of the vertebrate CTCF protein and several well- characterized C2H2 proteins in Drosophila and mammals.

Repression of the miR-627-5p by histone deacetylase 3 contributes to hypoxia-induced hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is one of the most common solid tumors globally. Our previous studies revealed that miR-627-5p suppresses HCC progression via targeting BCL3/CCND1 pathway. However, the molecular mechanism by which miR-627-5p was downregulated in HCC remains to be further elucidated. As a hallmark of solid tumors, hypoxia results in the rapid growth, strongly potential invasion and high frequent metastasis of cancer cells. Hypoxia-inducible factors (HIFs), mainly including HIF-1 and HIF-2, are the classical transcription factors which mediate hypoxia-related gene transcription. Here, we demonstrated that miR-627-5p was repressed by hypoxia in a HIF-1-dependent manner in HCC cells. But HIF-1 regulated miR-627-5p expression not directly through the hypoxia-response element (HRE) sites of MIR627 gene. In contrast, histone deacetylase 3 (HDAC3) was identified as a HIF-1 target gene, and the occupancy of HIF-1 to HRE site was essential for hypoxia-mediated HDAC3 induction. And upregulated HDAC3 was closely related to the malignant clinical and pathological characteristics and worse prognosis of HCC. Furthermore, HDAC3-mediated histone deacetylation in promoter region of MIR627 was critical for hypoxia-mediated miR-627-5p repression. And miR-627-5p mediated the effects of hypoxic condition on HCC progression. Thus, this study has revealed that miR-627-5p was repressed by hypoxia under the mediation of HDAC3 in HCC, and there existed a HIF-1α/HDAC3/miR-627-5p/BCL3/CCND1 signal pathway in HCC.

Genome-wide mining of wheat B-BOX zinc finger (BBX) gene family provides new insights into light stress responses

The B-BOX (BBX) proteins are an important class of zinc-finger transcription factors involved in the regulation of plant growth and development, and have been identified in many plant species. However, there is no systematic study of common wheat (Triticum aestivum L.) BBX genes. Through comprehensive bioinformatics analysis, we identified and characterised 96 BBX genes from wheat, and provided the genes with a unified nomenclature. We describe the chromosomal location, gene structure, conserved domains, phylogenetic relationships and promoter cis-elements of TaBBX family members. The expression patterns under different conditions, especially under different hormones and light–dark conditions, were studied in detail. According to the diversity of conserved domains, we divided TaBBX proteins into five subfamilies. Gene-duplication analysis showed that duplication of chromosome segments was the main reason for the expansion of the TaBBX gene family. Detecting the expression profiles of six TaBBX genes in different tissues by quantitative real-time PCR, we found that the six genes are regulated under light–dark treatment, and that some TaBBX genes (TaBBX2.11, TaBBX2.13, TaBBX2.15 and TaBBX3.10) are strongly induced by the plant hormones abscisic acid, indole-3-acetic acid and salicylic acid. Our analysis of wheat BBX genes at the genomic level will provide a solid foundation for further identifying the functions of specific genes in light stress responses.

Emerging role of pioneer transcription factors in targeted ERα positive breast cancer.

Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer factors” are an emerging class of TFs that specifically interact with nucleosomal DNA and facilitate accessible genomic binding sites for the additional TFs. There is growing evidence of these specialized modulators in particular malignancies, as highlighted by agents’ clinical efficacy, specifically targeting nuclear hormone receptors. They have been implicated in multiple cancers more recently, with a high proportion inculpating on hormone influential cancers. Moreover, extended crosstalk and cooperation between ERα pioneering factors in estrogen-dependent breast cancer (BC) remain elucidated. This review discusses on the recent advances in our understanding of pioneer TFs in cancer, especially highlighting its potentiality to modulate chromatin condensation to permit ERα recruitment in BC cells. Through the study it was concluded that the highly prospected pioneer TFs in BC, including FOXA1, TLE1, PBX1, and GATA3, possess the potential therapeutic significance and further innovations in the field could yield targeted therapy in cancer treatment.

The Pros and Cons of Circular RNAs as miRNA Sponges

The roles that noncoding RNAs play in various cells have been a focus of intense research in recent years. Circular RNAs (circRNAs) are noncoding RNAs that were initially thought to be junk by-products of splicing. Many circRNAs have been found to demonstrate important regulatory functions and, in particular, to act as miRNA sponges. The function of an miRNA sponge was compared with the function of a classic transcription factor (TF)-dependent regulatory loop in terms of efficiency, working rate, and noise characteristics. A circRNA with multiple binding sites for miRNA was found to act more efficiently than a TF and the respective loop worked faster, but only when the binding sites were not fully saturated with miRNA molecules. The noise characteristics of the circRNA loop were significantly worse with an increasing number of binding sites. A circRNA with one binding site was shown to be inefficient as an miRNA sponge. The circRNA-mediated regulation was assumed to provide a specific tool to the cell.

Genome-Wide Identification of the YABBY Gene Family in Seven Species of Magnoliids and Expression Analysis in Litsea

The YABBY gene family, specific to seed plants, encodes a class of transcription factors in the lamina maintenance and development of lateral organs. Magnoliids are sisters to the clade-containing eudicots and monocots, which have rapidly diversified among the common ancestors of these three lineages. However, prior to this study, information on the function of the YABBY genes in magnoliids was extremely limited to the third major clades and the early diverging lineage of Mesangiospermae. In this study, the sum of 55 YABBY genes including five genes in INO, six in CRC, eight in YAB2, 22 in YAB5, and 14 in FIL clade were identified from seven magnoliid plants. Sequence analysis showed that all encoded YABBY protein sequences possess the highly conserved YABBY domain and C2C2 zinc-finger domain. Gene and protein structure analysis indicates that a certain number of exons were highly conserved and similar in the same class, and YABBY genes encode proteins of 71–392 amino acids and an open reading frame of 216–1179 bp in magnoliids. Additionally, the predicted molecular weight and isoelectric point of YABBY proteins in three species ranged from 7689.93 to 43578.13 and from 5.33 to 9.87, respectively. Meanwhile, the YABBY gene homolog expression of Litsea was detected at a temporal and spatial level during various developmental stages of leaf and reproductive tissues. This research could provide a brief overview of YABBY gene family evolution and its differential expression in magnoliids. Therefore, this comprehensive diversification analysis would provide a new insight into further understanding of the function of genes in seven magnoliids.

Antibiotic binding releases autoinhibition of the TipA multidrug-resistance transcriptional regulator

Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic-binding TipAS effector domain in the apo state. We observed that the α6–α7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic-binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding but undergoes a remarkable conformational shift upon antibiotic binding to release this autoinhibition via a switch of its α6–α7 region. Hence, the promoters for MDR genes including tipA and RNA polymerases become available for transcription, enabling efficient antibiotic resistance. These insights into the molecular mechanism of activation of TipA proteins advance our understanding of TipA proteins, as well as bacterial MDR systems, and may provide important clues to block bacterial resistance.

Transcriptional integration of plant responses to iron availability.

Iron is one of the most important micronutrients for plant growth and development. It functions as the enzyme cofactor or component of electron transport chains in various vital metabolic processes, including photosynthesis, respiration, and amino acid biosynthesis. To maintain iron homeostasis, and therefore prevent any deficiency or excess that could be detrimental, plants have evolved complex transcriptional regulatory networks to tightly control iron uptake, translocation, assimilation, and storage. These regulatory networks are composed of various transcription factors; among them, members of the basic helix-loop-helix (bHLH) family play an essential role. Here, we first review recent advances in understanding the roles of bHLH transcription factors involved in the regulatory cascade controlling iron homeostasis in the model plant Arabidopsis, and extend this understanding to rice and other plant species. The importance of other classes of transcription factors will also be discussed. Second, we elaborate on the post-translational mechanisms involved in the regulation of these regulatory networks. Finally, we provide some perspectives on future research that should be conducted in order to precisely understand how plants control the homeostasis of this micronutrient.

The Multifaceted Output of c-Jun Biological Activity: Focus at the Junction of CD8 T Cell Activation and Exhaustion.

c-Jun is a major component of the dimeric transcription factor activator protein-1 (AP-1), a paradigm for transcriptional response to extracellular signaling, whose components are basic-Leucine Zipper (bZIP) transcription factors of the Jun, Fos, activating transcription factor (ATF), ATF-like (BATF) and Jun dimerization protein 2 (JDP2) gene families. Extracellular signals regulate c-Jun/AP-1 activity at multiple levels, including transcriptional and posttranscriptional regulation of c-Jun expression and transactivity, in turn, establishing the magnitude and the duration of c-Jun/AP-1 activation. Another important level of c-Jun/AP-1 regulation is due to the capability of Jun family members to bind DNA as a heterodimer with every other member of the AP-1 family, and to interact with other classes of transcription factors, thereby acquiring the potential to integrate diverse extrinsic and intrinsic signals into combinatorial regulation of gene expression. Here, we review how these features of c-Jun/AP-1 regulation underlie the multifaceted output of c-Jun biological activity, eliciting quite distinct cellular responses, such as neoplastic transformation, differentiation and apoptosis, in different cell types. In particular, we focus on the current understanding of the role of c-Jun/AP-1 in the response of CD8 T cells to acute infection and cancer. We highlight the transcriptional and epigenetic regulatory mechanisms through which c-Jun/AP-1 participates in the productive immune response of CD8 T cells, and how its downregulation may contribute to the dysfunctional state of tumor infiltrating CD8 T cells. Additionally, we discuss recent insights pointing at c-Jun as a suitable target for immunotherapy-based combination approaches to reinvigorate anti-tumor immune functions.

Innovation of heterochromatin functions drives rapid evolution of essential ZAD-ZNF genes in Drosophila.

Contrary to dogma, evolutionarily young and dynamic genes can encode essential functions. We find that evolutionarily dynamic ZAD-ZNF genes, which encode the most abundant class of insect transcription factors, are more likely to encode essential functions in Drosophila melanogaster than ancient, conserved ZAD-ZNF genes. We focus on the Nicknack ZAD-ZNF gene, which is evolutionarily young, poorly retained in Drosophila species, and evolves under strong positive selection. Yet we find that it is necessary for larval development in D. melanogaster. We show that Nicknack encodes a heterochromatin-localizing protein like its paralog Oddjob, also an evolutionarily dynamic yet essential ZAD-ZNF gene. We find that the divergent D. simulans Nicknack protein can still localize to D. melanogaster heterochromatin and rescue viability of female but not male Nicknack-null D. melanogaster. Our findings suggest that innovation for rapidly changing heterochromatin functions might generally explain the essentiality of many evolutionarily dynamic ZAD-ZNF genes in insects.